[HTML][HTML] Protective efficacy of a global HIV-1 mosaic vaccine against heterologous SHIV challenges in rhesus monkeys

DH Barouch, KE Stephenson, EN Borducchi, K Smith… - Cell, 2013 - cell.com
DH Barouch, KE Stephenson, EN Borducchi, K Smith, K Stanley, AG McNally, J Liu…
Cell, 2013cell.com
The global diversity of HIV-1 represents a critical challenge facing HIV-1 vaccine
development. HIV-1 mosaic antigens are bioinformatically optimized immunogens designed
for improved coverage of HIV-1 diversity. However, the protective efficacy of such global HIV-
1 vaccine antigens has not previously been evaluated. Here, we demonstrate the capacity of
bivalent HIV-1 mosaic antigens to protect rhesus monkeys against acquisition of infection
following heterologous challenges with the difficult-to-neutralize simian-human …
Summary
The global diversity of HIV-1 represents a critical challenge facing HIV-1 vaccine development. HIV-1 mosaic antigens are bioinformatically optimized immunogens designed for improved coverage of HIV-1 diversity. However, the protective efficacy of such global HIV-1 vaccine antigens has not previously been evaluated. Here, we demonstrate the capacity of bivalent HIV-1 mosaic antigens to protect rhesus monkeys against acquisition of infection following heterologous challenges with the difficult-to-neutralize simian-human immunodeficiency virus SHIV-SF162P3. Adenovirus/poxvirus and adenovirus/adenovirus vector-based vaccines expressing HIV-1 mosaic Env, Gag, and Pol afforded a significant reduction in the per-exposure acquisition risk following repetitive, intrarectal SHIV-SF162P3 challenges. Protection against acquisition of infection correlated with vaccine-elicited binding, neutralizing, and functional nonneutralizing antibodies, suggesting that the coordinated activity of multiple antibody functions may contribute to protection against difficult-to-neutralize viruses. These data demonstrate the protective efficacy of HIV-1 mosaic antigens and suggest a potential strategy for the development of a global HIV-1 vaccine.
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